Have you or your loved ones been diagnosed with acute biphenotypic leukemia?
You may be eligible to participate in a acute biphenotypic leukemia clinical trial.
Have you or your loved ones been diagnosed with acute biphenotypic leukemia? You may be eligible to participate in a acute biphenotypic leukemia clinical trial.
What is a clinical trial? Is participating in a clinical trial right for you? Learn more
Acute Biphenotypic Leukemia Clinical Trial in Seattle WA
Have you or your loved ones been diagnosed with acute biphenotypic leukemia?
You may be eligible to participate in a acute biphenotypic leukemia clinical trial.
Have you or your loved ones been diagnosed with acute biphenotypic leukemia? You may be eligible to participate in a acute biphenotypic leukemia clinical trial.
Terminated
Male & Female
All ages
This phase II trial studies how well donor peripheral blood stem cell (PBSC) transplant works in treating patients with hematologic malignancies. Cyclophosphamide when added to tacrolimus and mycophenolate mofetil is safe and effective in preventing severe graft-versus-host disease (GVHD) in most patients with hematologic malignancies undergoing transplantation of bone marrow from half-matched (haploidentical) donors. This approach has extended the transplant option to patients who do not have matched related or unrelated donors, especially for patients from ethnic minority groups. The graft contains cells of the donor's immune system which potentially can recognize and destroy the patient's cancer cells (graft-versus-tumor effect). Rejection of the donor's cells by the patient's own immune system is prevented by giving low doses of chemotherapy (fludarabine phosphate and cyclophosphamide) and total-body irradiation before transplant. Patients can experience low blood cell counts after transplant. Using stem cells and immune cells collected from the donor's circulating blood may result in quicker recovery of blood counts and may be more effective in treating the patient's disease than using bone marrow.
Details for the study
Brief Title
Donor Peripheral Blood Stem Cell Transplant in Treating Patients With Hematologic Malignancies
Official Title
Nonmyeloablative Hematopoietic Cell Transplantation (HCT) for Patients With Hematologic Malignancies Using Related, HLA-Haploidentical Donors: A Phase II Trial of Peripheral Blood Stem Cells (PBSC) as the Donor Source
Brief Summary
This phase II trial studies how well donor peripheral blood stem cell (PBSC) transplant works <br /> in treating patients with hematologic malignancies. Cyclophosphamide when added to tacrolimus <br /> and mycophenolate mofetil is safe and effective in preventing severe graft-versus-host <br /> disease (GVHD) in most patients with hematologic malignancies undergoing transplantation of <br /> bone marrow from half-matched (haploidentical) donors. This approach has extended the <br /> transplant option to patients who do not have matched related or unrelated donors, especially <br /> for patients from ethnic minority groups. The graft contains cells of the donor's immune <br /> system which potentially can recognize and destroy the patient's cancer cells <br /> (graft-versus-tumor effect). Rejection of the donor's cells by the patient's own immune <br /> system is prevented by giving low doses of chemotherapy (fludarabine phosphate and <br /> cyclophosphamide) and total-body irradiation before transplant. Patients can experience low <br /> blood cell counts after transplant. Using stem cells and immune cells collected from the <br /> donor's circulating blood may result in quicker recovery of blood counts and may be more <br /> effective in treating the patient's disease than using bone marrow.
Detailed Description
PRIMARY OBJECTIVES:
I. To demonstrate that use of PBSC in place of marrow as the source of lymphocytes and stem
cells for nonmyeloablative transplants from related, haploidentical donors will not result in
unacceptable rates of high-grade acute or chronic GVHD, non-relapse mortality or relapse
compared to historical data on nonmyeloablative transplants from unrelated donors.
SECONDARY OBJECTIVES:
I. Estimates of the rates of neutrophil and platelet recovery, number of red blood cell (RBC)
and platelet transfusions, incidences of graft failure, transplant-related toxicities,
disease-free survival and overall survival.
OUTLINE:
Patients receive fludarabine intravenously (IV) over 30-60 minutes daily on days -6 through
-2 and cyclophosphamide IV over 1-2 hours on days -6, -5, and 3-4. Patients undergo
total-body irradiation on day -1. Patients undergo donor peripheral blood stem cell
transplant on day 0. Patients then receive tacrolimus IV once daily or orally (PO) twice
daily (BID) on days 5-180 (may be continued if active GVHD is present), mycophenolate mofetil
IV or PO thrice daily (TID) on days 5-35 (may be continued if GVHD present), and filgrastim
IV beginning on day 5 until the absolute neutrophil count (ANC) is >= 1,000/mm^3 for three
consecutive days.
Treatment continues in the absence of disease progression or unacceptable toxicity.
Treatments and/or Procedures
Filgrastim
Given SQ
Tacrolimus
Given IV or PO
Cyclophosphamide
Given IV
Mycophenolate mofetil
Given PO
Fludarabine phosphate
Given IV
Nonmyeloablative allogeneic hematopoietic stem cell transplantation
Undergo PBSC
Peripheral blood stem cell transplantation
Undergo PBSC
Total Body Irradiation
Undergo total-body irradiation (TBI)
Outcome Measures
Outcome measures are the tests that investigators perform to prove whether or not a treatment being tested in a clinical trial is having any effect.
Primary
Relapse of Malignancy After Transplantation
Defined by either morphological or cytogenetic evidence of acute leukemia consistent with pre-transplant features, or radiologic evidence of lymphoma progression. When in doubt, the diagnosis of recurrent or progressive lymphoma should be documented by tissue biopsy.
Primary
Incidence of Grades III/IV Acute Graft Versus Host Disease
Grading determined by organ system stages. Grade III/IV acute graft versus host disease is defined as skin: stage IV, liver: stages II-IV, and/or gastrointestinal tract: stages II-IV.
Primary
Percentage of Participants With Chronic Graft Versus Host Disease
Scored according to the National Cancer Institute criteria. Mild-to-severe chronic GVHD at 2 years.
Primary
Non-relapse Mortality at 1 Year
Cumulative incidence of death without evidence of disease progression at 1 year
Secondary
Point Estimate of Overall Survival at 3 Years
Kaplan Meier estimate of the percentage of participants with overall survival at 3 years
Secondary
Number of Platelet Transfusions
Number platelet transfusions given to the patient between day 0 and day 100 post transplant
Secondary
Number of Red Blood Cell Transfusions
Number of units of RBCs given to the patient between day 0 and day 100 post transplant
Secondary
Toxicity of Treatment Regimen Determined by Number of Adverse Events Per Organ System
Assessed by Common Terminology Criteria for Adverse Events version 3.0. The incidence of all adverse events greater or equal to grade 3 was determined.
Secondary
Time to Neutrophil Recovery
Achievement of an absolute neutrophil count greater or equal to 500/mm^3 for three consecutive measurements on different days. The first of the three days will be designated the day of neutrophil recovery.
Secondary
Incidence of Primary Graft Failure
Defined as < 5% donor CD3 chimerism. Chimerism will be measured by short tandem repeat-polymerase chain reaction on peripheral blood sorted into CD3 and CD33 cell fractions.
Secondary
Time to Platelet Recovery
The first day of a sustained platelet count > 20,000/mm^3 with no platelet transfusions in the preceding seven days.
Secondary
Disease-free Survival
Defined as being alive and in remission by < 5% blasts by bone marrow morphology for patients with myeloid malignancies and CT or PET imaging for patients with lymphoid malignancies at the time of the assessment
Study Criteria
Inclusion Criteria:
- Molecular based human leukocyte antigen (HLA) typing will be performed for the HLA-A,
-B, -Cw, -DRB1 and -DQB1 loci to the resolution adequate to establish haplo-identity;
a minimum match of 5/10 is required; an unrelated donor search is not required for a
patient to be eligible for this protocol if the clinical situation dictates an urgent
transplant; clinical urgency is defined as 6-8 weeks from referral or low-likelihood
of finding a matched, unrelated donor
- Acute leukemias (includes T lymphoblastic lymphoma); remission is defined as < 5%
blasts with no morphological characteristics of acute leukemia (e.g., Auer rods) in a
bone marrow with > 20% cellularity, peripheral blood counts showing ANC > 1000/ul,
including patients in complete remission with incomplete platelet recovery (CRp); if
the marrow has < 20% cellularity due to treatment related cytotoxicity, but still has
< 5% blasts, an exception may be made to include this patient up to principal
investigator (PI) discretion
- Acute lymphoblastic leukemia in high risk first complete remission (CR1) as defined by
at least one of the following:
- Adverse cytogenetics including but not limited to t(9;22), t(1;19), t(4;11),
mixed lineage leukemia (MLL) rearrangements
- White blood cell counts > 30,000/mcL
- Patients over 30 years of age
- Time to complete remission > 4 weeks
- Presence of extramedullary disease
- Minimal residual disease
- Other risk factors determined by the patient's attending physician to be high
risk features requiring transplantation
- Acute myelogenous leukemia in high risk CR1 as defined by at least one of the
following:
- Greater than 1 cycle of induction therapy required to achieve remission
- Preceding myelodysplastic syndrome (MDS)
- Presence of fms-like tyrosine kinase receptor-3 (Flt3) abnormalities
- French-American-British (FAB) M6 or M7 leukemia, or
- Adverse cytogenetics for overall survival such as:
- Those associated with MDS
- Complex karyotype (>= 3 abnormalities); or
- Any of the following: inv(3) or t(3;3), t(6;9), t(6;11), + 8 [alone or with
other abnormalities except for t(8;21), t(9;11), inv(16) or t(16;16)],
t(11;19)(q23;p13.1)]
- Other risk factors determined by the patient's attending physician to be high
risk features requiring transplantation
- Acute leukemias in second (2nd) or subsequent remission
- Biphenotypic/undifferentiated leukemias in first (1st) or subsequent complete
remission (CR)
- High-risk MDS status-post cytotoxic chemotherapy
- Burkitt's lymphoma: second or subsequent CR
- Chemotherapy-sensitive (at least stable disease) large cell, mantle cell or Hodgkin's
lymphomas that have failed at least 1 prior regimen of multi-agent chemotherapy and
are ineligible for an autologous transplant
- Marginal zone B-cell lymphoma or follicular lymphoma that has progressed after at
least two prior therapies (excluding single agent Rituxan)
- Multiple myeloma (MM) stage II or III patients who have progressed after an initial
response to chemotherapy or autologous hematopoietic stem cell transplantation (HSCT)
or MM patients with refractory disease who may benefit from tandem
autologous-nonmyeloablative allogeneic transplant
- Left ventricular ejection fraction at rest must be >= 35%
- Bilirubin =< 2.5 mg/dL
- Alanine aminotransferase (ALT) < 5 x upper limit of normal (ULN)
- Aspartate aminotransferase (AST) < 5 x ULN
- Alkaline phosphatase < 5 x ULN
- Serum creatinine within normal range for age, or if serum creatinine outside normal
range for age, then renal function (creatinine clearance or glomerular filtration rate
[GFR]) > 40 mL/min/1.73m^2
- Forced expiratory volume in one second (FEV1), forced vital capacity (FVC), diffusion
capacity of carbon monoxide (DLCO) (diffusion capacity) >= 40% predicted (corrected
for hemoglobin); if unable to perform pulmonary function tests, then oxygen (O2)
saturation > 92% on room air
- Karnofsky/Lansky score >= 60%
- Patients who have received a prior allogeneic HSCT and who have either rejected their
grafts or who have become tolerant of their grafts with no active GVHD requiring
immunosuppressive therapy
- Patients will undergo standard pre-transplant work-up as dictated by standard practice
guidelines the results of which may be used for screening for this study
- DONOR: Donors must be HLA-haploidentical first-degree relatives of the patient;
eligible donors include biological parents, siblings, or children, or half-siblings
- DONOR: Age >= 12 years
- DONOR: Weight >= 40 kg
- DONOR: Ability of donors < 18 years of age to undergo apheresis without use of a
vascular access device; vein check must be performed and verified by an apheresis
nurse prior to arrival at the Seattle Cancer Care Alliance (SCCA)
- DONOR: Donors must meet the selection criteria as defined by the Foundation for the
Accreditation of Cell Therapy (FACT) and will be screened per the American Association
of Blood Banks (AABB) guidelines
Exclusion Criteria:
- HLA-matched or single allele-mismatched donor able to donate
- Pregnancy or breast-feeding
- Current uncontrolled bacterial, viral or fungal infection (currently taking medication
with evidence of progression of clinical symptoms or radiologic findings)
- Patients with primary idiopathic myelofibrosis
- DONOR: Positive anti-donor HLA antibody